CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor

Qin, Xiaoying; Wang, Y.; Li, G.-X.; Qin, Ya‐Zhen; Wang, F.-R.; Xu, Lei; Chen, H.; Wang, Han; Wang, J.-Z.; Zhang, X.-H.; Chang, Ying‐Jun; Liu, K.-Y.; Zhao, Jiang; Huang, Xiao Jun

doi:10.1186/s12967-016-0864-2

Cited by 12 publications

(23 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After browsing relevant literatures about issues in this aspect, we found discrepant results as well. As for the polymorphism of +49 at exon 1, the same tendency to cGVHD was observed in studies by Azarian et al [16] and Sellami et al [19], conversely, Mossalam et al [24], Vannucchi et al [17] and Qin et al [26] found that +49 G allele in donor was not associated with cGVHD risk. In addition, the data provided by Perez-Garcia et al [15] in a Spanish cohort indicated that the presence of donor CT60 GG + AG resulted in a reduction of moderate GVHD (II-IV) incidence, which is completely contradicted with that concluded by Xiao et al [23].…”

Section: Discussionsupporting

confidence: 69%

“…Cunha et al [27] also revealed the same conclusion regarding the CTLA-4 CT60 polymorphism, suggesting the GG genotype reduced the OS in patients after CBT. As for +49 A/G, Qin et al [26] supported the abovementioned results, whereas the contrary findings were presented by Piccioli et al [18], who observed a longer OS in patients transplanted from a donor that was homozygote G/G. Several other studies did not observe any significant influence of donor +49 or CT60 genetic polymorphism on OS in different cohorts [16,17,24].…”

Section: Discussionmentioning

confidence: 86%

See 1 more Smart Citation

Association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) single nucleotide polymorphism in donors with clinical outcome after allogeneic hematopoietic stem cell transplantation: a meta-analysis

Wang

Zhang

et al. 2021

Hematology

View full text Add to dashboard Cite

Objective: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) polymorphisms at positions of +49 and CT60 in donors have been reported to influence clinical outcome following allogeneic hematopoietic stem cell transplantation (allo-HSCT), such as overall survival (OS), disease free survival (DFS), relapse and the risk of graft versus host disease (GVHD). However, the results still remain controversial. Thus, we conducted the first meta-analysis to get a more accurate estimation of the relationship between CTLA-4 genotype and the above end points. Methods: PubMed, Embase, Web of science and Cochrane Library were searched to select eligible studies, data were extracted and then combined ORs/HRs together with the corresponding 95% confidence intervals (CIs) were calculated. Both the dominant and recessive models were employed to evaluate the associations between genetic variation in donor CTLA-4 and outcome after allo-HSCT. Results: A total of 15 studies were included the pooled results indicated that +49 GG homozygote in donors was significantly associated with increased risk of chronic GVHD (OR=1.701, 95% CI, 1.124-2.573, P=0.012, I 2 =34.7%). With regard to CT60 polymorphism, donors with G allele correlated with worse OS (HR = 1.422, 95% CI, 1.080-1.872, P=0.012, I 2 =0%) and lower susceptibility to severe acute GVHD (HR=0.619, 95% CI, 0.426-0.899, P=0.012, I 2 =0%). There was no significant association between CTLA-4 polymorphism and DFS or the incidence of relapse. Conclusions: The present meta-analysis suggests that donors with CT60 G allele might be associated with worse OS but reduced severe aGVHD occurrence, while patients transplanted from donors with GG genotype at position of +49 are more likely to suffer from cGVHD.

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 86%

Association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) single nucleotide polymorphism in donors with clinical outcome after allogeneic hematopoietic stem cell transplantation: a meta-analysis

Wang

Zhang

et al. 2021

Hematology

View full text Add to dashboard Cite

show abstract

“…Similar discrepancies are present when scrutinising the donor +49 A/G (rs231775) polymorphism. Qin et al have found that the GG donor genotype is associated with lower overall survival [ 68 ], while Hammrich et al state that the AA donor genotype is associated with higher relapse rate and worse event-free survival [ 70 ]. Moreover, the G donor allele is believed to be associated with a higher risk of chronic GVHD; −318 C/T (rs5742909) has been investigated in one study to date, and a weak association has been found for the TT donor genotype and higher risk of disease relapse.…”

Section: Discussionmentioning

confidence: 99%

“…Mossallam and Samra checked the influence of +49 A/G on 80 patients and found the following association: recipients with the G allele had lower survival indicators than people with the AA genotype [ 67 ]. Another association concerning +49 A/G was found in a group of 152 patients, where the donor GG genotype was a risk factor for lower overall survival [ 68 ].…”

Section: The Role Of Ctla4 and Its Polymorphisms In Allogeneic Haementioning

confidence: 99%

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation

Rosik

Szostak

Machaj

et al. 2021

IJMS

View full text Add to dashboard Cite

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and -318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the -1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.

show abstract

“…A genome-wide association study has revealed that rs13202464, instead of rs4349859, within the MHC region represents the main risk effect of HLA-B*27 variants in Han Chinese ( Cortes et al, 2013 ). In addition to the SNPs flanking the HLA loci, many SNPs beyond chromosome 6, where the HLA loci are located, are related to relapse after HSCT ( Dickinson & Charron, 2005 ; Qin et al, 2016 ; Wun et al, 2017 ; Berro et al, 2017 ). The SNPs within the tumor necrosis factor II receptor superfamily member 1B gene and the interleukin 10 gene in human chromosome 1 are associated with improved survival after HSCT ( Dickinson et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms within HLA region are associated with disease relapse for patients with unrelated cord blood transplantation

Chen

Chang

Jaing

et al. 2018

PeerJ

View full text Add to dashboard Cite

Disease relapse occurs in unrelated cord blood transplantation (CBT) even when the alleles of human leukocyte antigen (HLA) are fully matched between donor and recipient. This is similar to that observed in other types of hematopoietic stem cell transplantation. Fourteen single nucleotide polymorphisms (SNPs) within the HLA region have been reported previously by Petersdorf et al. and Piras et al. as transplantation determinants in unrelated hematopoietic cell transplantation. In this study, the genomic sequences within 500 base pairs upstream and downstream of the fourteen transplantation-related SNPs from 53 patients and their HLA-matched unrelated donors were analyzed for determining whether or not genetic variants, conferred by either recipient or donor SNP genotype or by recipient-donor SNP mismatching, were associated with the risk of relapse. Seven SNPs were associated with the risk of relapse in unrelated CBT. These included the donor genotype with the SNPs of rs2523675 and rs2518028 at the telomeric end of HCP5 gene, rs2071479 in the intron of the HLA-DOB gene, and rs2523958 in the MICD gene; and the recipient genotype with SNPs of rs9276982 in the HLA-DOA gene, and rs435766 and rs380924 in the MICD gene. As measured by pair-wise linkage disequilibrium (LD) with D′ as the parameter for normalized standard measurement of LD which compares the observed and expected frequencies of one haplotype comprised by alleles at different loci, rs2523675 had high LD with rs4713466 (D′ = 0.86) and rs2523676 (D′ = 0.91) in the HCP5 gene. The rs2518028 had no LD with all other SNPs except rs2523675 (D′ = 0.76). This study provides the basis for developing a method or algorithm for selecting better unrelated CBT candidate donors.

show abstract

CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor

Cited by 12 publications

References 56 publications

Association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) single nucleotide polymorphism in donors with clinical outcome after allogeneic hematopoietic stem cell transplantation: a meta-analysis

Association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) single nucleotide polymorphism in donors with clinical outcome after allogeneic hematopoietic stem cell transplantation: a meta-analysis

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation

Single nucleotide polymorphisms within HLA region are associated with disease relapse for patients with unrelated cord blood transplantation

Contact Info

Product

Resources

About